DHEA Supplementation: Risks and Benefits
Primary Recommendation
DHEA supplementation at 25 mg daily can be offered to specific patient populations—particularly postmenopausal women with vaginal atrophy/sexual dysfunction and women with adrenal insufficiency experiencing persistent low libido or energy—but should be used cautiously given limited long-term safety data and potential hormone-dependent cancer risks. 1, 2, 3
Established Clinical Benefits
Female Sexual Dysfunction and Vaginal Atrophy
- Intravaginal DHEA represents the most evidence-based indication, showing significant improvements in vaginal dryness, dyspareunia, sexual desire, arousal, pain, and overall sexual function in postmenopausal women 2, 3
- Clinical trials in female cancer survivors demonstrated significant improvements across multiple domains of sexual function 1
- The American College of Obstetricians and Gynecologists recommends 25 mg orally once daily in the morning for postmenopausal women with vaginal atrophy, low libido, or low energy 2
Adrenal Insufficiency
- Women with primary adrenal insufficiency experiencing persistent low libido or energy despite optimized glucocorticoid/mineralocorticoid replacement should receive 25 mg DHEA daily 2, 3
- Treatment should only be continued if clinically effective after a 6-month trial period 1, 2
Other Potential Benefits (Less Established)
- In elderly populations, DHEA may improve physical and psychological well-being, muscle strength, bone density, and reduce body fat and age-related skin atrophy 4
- Immunomodulatory effects include increased monocytes, T cells, and natural killer cells 4
- May be steroid-sparing in systemic lupus erythematosus 4
Dosing Protocol
Standard Dosing
- Starting dose: 25 mg orally once daily in the morning 1, 2, 3
- Dose range can be adjusted between 10-50 mg daily based on clinical response 1, 2, 3
Monitoring Requirements
- Establish baseline hormone levels before initiating therapy (DHEA sulfate, androstenedione, testosterone) 1, 2
- Follow-up hormone measurements should be taken in the morning before DHEA ingestion 1
- Serum levels should be maintained in the normal range 1
- Evaluate treatment effect after 3-6 months 2
Treatment Duration
- Implement a 6-month trial period before determining long-term use 1, 2
- Continue therapy only if patient reports subjective improvement in target symptoms 2
- Consider limiting therapy to 24 months due to limited long-term safety data 2
Major Risks and Contraindications
Hormone-Dependent Cancers
- DHEA is generally contraindicated in breast cancer survivors due to potential risks of hormone-dependent cancers 2, 3
- Should be used with extreme caution in patients receiving aromatase inhibitor therapy, as vaginal DHEA increases circulating androgen levels 1, 2, 3
- For women with hormone-positive breast cancer on aromatase inhibitors who have not responded to lubricants and moisturizers, vaginal DHEA may be offered only after thorough discussion of risks and benefits 2
- Women with BRCA1/2 mutations without personal history of breast cancer may consider DHEA after prophylactic bilateral salpingo-oophorectomy 2
- Men with breast cancer should not use DHEA 3
Reproductive Effects
- DHEA should not be prescribed to men currently trying to conceive, as it can suppress normal sperm production 1
Long-Term Safety Concerns
- Long-term effects of DHEA replacement therapy are not fully known, requiring cautious use 1, 2, 3
- No large-scale, long-term controlled trials have definitively established safety profiles 5, 6
Androgenic Side Effects
- Monitor for signs of virilization (acne, oily skin, hirsutism), which indicate excessive androgen exposure requiring immediate dose adjustment 2
- For women on concurrent hormone therapy, recognize that DHEA and testosterone have additive effects—monitor total androgen levels carefully 2
Quality Control Concerns
- Because DHEA is classified as a "nutritional supplement," it is not subjected to government regulation 6
- Potential exists for inaccurate dosage and impurities across different brands 6, 7
- Different brands may contain different amounts of active ingredient 7
Evidence Limitations and Conflicting Data
Cognitive Function and Well-Being
- A Cochrane review found limited support for improvement in well-being, with effects only reported in longer-term studies using crude measures 5
- The same review found no support for improvement in memory or cognitive function, though cognitive function was only measured in short-duration trials 5
- One review noted improvements in psychological well-being in elderly populations, but results remain inconsistent 4
Cardiovascular Effects
- Low DHEA/DHEAS levels correlate with increased cardiovascular disease and all-cause mortality 4
- DHEA modulates cardiovascular signaling pathways with anti-inflammatory and vasorelaxant effects 4
- However, discrepant results exist regarding the association between DHEA levels and coronary artery disease 6
Metabolic and Immune Effects
- Studies show potential benefits in immune function, but clinical significance remains unknown 6
- May improve insulin sensitivity in adrenal insufficiency 4
- Results regarding metabolic benefits are inconsistent across studies 8
Common Pitfalls to Avoid
- Do not prescribe DHEA without establishing baseline hormone levels 2
- Do not ignore signs of virilization—these indicate excessive androgen exposure requiring immediate dose adjustment 2
- Do not use DHEA in breast cancer survivors without thorough risk-benefit discussion and consideration of alternatives 2, 3
- Do not continue therapy beyond 6 months without documented clinical benefit 1, 2
- Do not assume all DHEA supplements contain accurate dosing—quality varies significantly 6, 7
Alternative Treatment Options
For female sexual dysfunction when DHEA is contraindicated or ineffective: